Ghilantens: anticoagulant-antimetastatic proteins from the South American leech, Haementeria ghilianii.
Five proteins with anticoagulant and antimetastatic activities were isolated from the salivary glands of the Amazon leech, Haementeria ghilianil. These proteins, designated ghilantens, were co-purified on DEAE-cellulose and heparin-agarose, and were purified by microbore C-18 reverse-phase HPLC. Each variant had a similar molecular weight (18,000), amino acid composition, and a blocked amino terminus. Ghilantens caused a dose-dependent prolongation of the prothrombin time of normal human plasma and blocked the factor Xa-mediated hydrolysis of methoxycarbonyl-D-cyclohexylglycyl-glycl-arginine-p-nitro anillide acetate. Ghilantens were quantitatively absorbed to bovine factor Xa-AffiGel-15 and were eluted with 0.1 mol/L benzamidine, an active-site reversible inhibitor of factor Xa. These findings show that ghilantens can form a reversible association with the enzyme. When administered intravenously to mice by tall vein injection, ghilantens potently suppressed lung metastases of B16-F10 melanoma cells. These findings suggest that ghilantens may have therapeutic value in the treatment of metastatic disease.
Brankamp
R G
RG
Merell Dow Research Institute, Cincinnati, OH 45215-6300.
Blankenship
D T
DT
Sunkara
P S
PS
Cardin
A D
AD
D000595:Amino Acid Sequence; D000818:Animals; D000925:Anticoagulants / Q000032:analysis / Q000302:isolation & purification*; D000970:Antineoplastic Agents / Q000032:analysis / Q000302:isolation & purification*; D007865:Leeches / Q000032:analysis*; D008969:Molecular Sequence Data; D012469:Salivary Glands / Q000032:analysis; D012471:Salivary Proteins and Peptides / Q000032:analysis / Q000302:isolation & purification*
D000925:Anticoagulants; D000970:Antineoplastic Agents; D012471:Salivary Proteins and Peptides